ASCC3 promotes the immunosuppression and progression of non-small cell lung cancer by impairing the type I interferon response via CAND1-mediated ubiquitination inhibition of STAT3.

"these results were further corroborated by a larger cohort analysis from the tcga database showing that high ascc3 expression (using a cut-off of the median expression value of 2 62) correlated with a worse probability of os ( online supplemental figure 1a ) 10 1136/jitc-2023-007766 supp1 supplementary data 10 1136/jitc-2023-007766 supp2 supplementary data table 1 correlations between ascc3 and clinicopathological features in 173 patients with non-small cell lung cancer characteristics number of patients p value ascc3 low ascc3 high age (years) mean?; collectively these findings indicated that ascc3 recruited cand1 to stat3 and that cand1 upregulated the protein level of stat3 by inhibiting the ub-mediated degradation of stat3 10 1136/jitc-2023-007766 supp4 supplementary data 10 1136/jitc-2023-007766 supp5 supplementary data figure 5 ascc3 recruits cand1 to stabilize stat3 in nsclc (a) cand1 could pull down ascc3 and stat3 (bc) co-ip assay confirmed that the interaction of ascc3 with cand1 and domain 5 of ascc3 (c-terminal 2) was responsible for their binding (de) if assay in both h1299 and h460 cells showed colocalization of cand1 and stat3 (f) ascc3 mutation (deletion in the c-terminal 2) impaired the interaction of cand1 and stat3 (g) in h1299- ascc3 mutant cells the expression of stat3 was downregulated and the colocalization of cand1 and stat3 decreased (hi) interference with cand1 decreased the protein level but did not influence the transcription of stat3 (j) mutation of ascc3 or interference of cand1 upregulated the ubiquitination level of stat3 and in ascc3-cand1 cells the ubiquitination level of stat3 was similar to that of ascc3-sicand1 cells that were administered the ubiquitination inhibitor mg-132 (10 um 48 hours) **p<0 01 ns: not significant."

"Competing interests: None declared."

"Funding: This research was funded by grants from the National Natural Science Foundation of China (81972168), Strategic Priority Research Program of the Chinese Academy of Sciences (XDB29030103) and National Key R&D Program of China (2021YFA1301402)."